Zhao et al. Radiation Oncology (2016):5
DOI 10.1186/s13014-016-0605-y
RESEARCH
Open Access
The efficacy of postoperative radiotherapy
in localized primary soft tissue sarcoma
treated with conservative surgery
Ru-Ping Zhao1†, Xiao-Li Yu2,3†, Zhen Zhang2,3, Li-Juan Jia4, Yan Feng2,3, Zhao-Zhi Yang2,3, Xing-Xing Chen2,3,
Jian Wang3,5, Sheng-Lin Ma6* and Xiao-Mao Guo2,3*
Abstract
Background: To evaluate the efficacy of postoperative radiotherapy (RT) on local failure-free survival (LFFS), distant
metastasis-free survival (DMFS) and overall survival (OS) in patients with localized primary soft tissue sarcoma (STS)
and to identify prognostic factors.
Methods and materials: Between January 2000 and July 2010, 220 consecutive patients with localized primary STS,
who received conservative surgery with or without postoperative RT, were enrolled in the study. Survival curves were
constructed by the Kaplan-Meier method and log-rank test was used to assess statistical significance. Multivariate analysis
was applied to identify the prognostic factors.
Results: After a median follow-up of 68 months (range, 5–127 months), the 5-year LFFS, DMFS and OS were 70.0, 78.2
and 71.2 %, respectively. Tumor size, histological subtypes, margin status and postoperative RT were independent
predictors for OS. Postoperative RT was associated with a significant reduced local recurrence risk versus surgery
alone (hazard ratio [HR] = 0.408, 95 % confidence interval [CI] 0.235–0.707, P = 0.001), with 5-year LFFS of 81.1 and
63.6 %, respectively (log-rank, P = 0.004). The log-rank test showed that postoperative RT had a tendency of improving
OS compared with surgery alone, with 5-year OS of 74.8 and 65.0 %, respectively (P = 0.089). Multivariate analysis
demonstrated that postoperative RT significantly reduced mortality rate compared with surgery alone (HR = 0.512,
95 % CI 0.296–0.886, p = 0.017), especially in patients with liposarcoma (p = 0.034).
Conclusion: Postoperative radiotherapy reduce both local recurrence and STS mortality in patients with localized
primary STS. The efficacy of RT on survival warrants further prospective study.
Keywords: Soft tissue sarcoma, Surgery, Radiotherapy, Local recurrence, Overall survival
Background
Soft tissue sarcomas (STS) are a heterogeneous group of
uncommon neoplasms arising from mesenchymal tissues,
accounting for less than 1 % of all malignancies [1]. The
conservative surgery is the most important primary treatment for patients with STS [2]. Close margin and even
positive margin may be needed to avoid amputation or
preserve critical neurovascular structures, which lead to
* Correspondence: [email protected]; [email protected]
†
Equal contributors
6
Department of Radiation Oncology, Hangzhou First People’s Hospital, 261
Huan Sha Road, Hangzhou, Zhejiang, China
2
Department of Radiation Oncology, Cancer Hospital of Fudan University,
270 Dong An Road, Xuhui, Shanghai, China
Full list of author information is available at the end of the article
high risk of local failure in the surgical bed. The data from
previous studies showed the local recurrence rate after
conservative surgery alone was up to 30 % [3, 4]. Randomized trials demonstrated that the addition of postoperative radiotherapy (RT) after conservative surgery
could further reduce local recurrence when compared
with surgery alone [5, 6]. Based on these studies,
conservative surgery plus RT became the mainstay
treatment modality in patients with STS.
Although randomized trials showed postoperative RT
significantly improved local control, the local control
benefit associated with RT did not translate into a
survival advantage. Even after 17 years of follow-up,
Beane JD et al. only demonstrated a trend toward improved
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Zhao et al. Radiation Oncology (2016):5
survival in the RT group that failed to reach statistical
significance. The authors acknowledged that their study
was underpowered to demonstrate a survival advantage
of <20 % [7]. This scenario has been replicated in several
retrospective series [8–10]. It was initially believed that
the improved local control by postoperative RT could only
enhance local control, while had no efficacy on survival in
patients with breast cancer. After accumulating the patients who treated with RT, The reports of the early Breast
Cancer Trialists’ Collaborative Group (EBCTCG) metaanalysis demonstrated that postoperative RT reduced the
incidence of breast cancer recurrence and mortality [11].
It is likely that previous studies were underpowered to definitively demonstrate a survival advantage with the use of
RT in patients with STS. Recently, several SEER analyses
and retrospective studies that including a large number of
STS reported that postoperative RT could also improve
the survival of STS [12–15]. The question still remains if
the improved local control with the use of RT can convert
to survival benefit or not. The impacts of RT on patients
with STS merit further investigation.
This paper summarized our experience with homogenous population of adult patients with STS, who
were treated by the conservative modality, either surgery
alone or surgery plus RT. The aim of the study is to
evaluate the impacts of RT on local failure-free survival
(LFFS) and distant metastasis-free survival (DMFS)
and overall survival. This study also evaluates the relationship between various clinicopathologic factors and
disease outcomes to identify the prognostic factors.
Methods/materials
Patients
We retrospectively reviewed 251 consecutive adult patients with localized primary STS during the period of
January 2000 to July 2010. We excluded those patients
with secondary sarcoma (n = 6), who received amputation or the treatment for palliative purpose (n = 8), surgically unresectable disease at presentation (n = 5), and
those without follow-up data (n = 12). The remaining
220 patients were represented in this study. Histological
diagnosis was confirmed in each case through review of
the slides by a pathologist. The Institutional Review
Board of Cancer Hospital of Fudan University approved
review of data for this investigation.
The French Federation of Cancer Centers grading system was used for tumor grading, which was determined
as low- (Grade I), intermediate- (Grade II) or high-grade
(Grade III) [16]. A negative margin was defined as the
absence of tumor at the inked margin. We reviewed the
medical records, including operative and pathologic reports, and recorded the following information: age, gender, tumor anatomic location, histopathological subtype,
Page 2 of 8
size, grade, surgical margins status, lymph node status,
treatment modality and toxicities.
Treatment
All patients were reviewed at an oncology multidisciplinary
board and underwent appropriate structure- and functionpreserving surgical resection. In patients with the tumor
adjacent to neurovascular bundles or critical structures, an
attempt was made to obtain gross tumor free margin.
Some patients received postoperative radiation and/or
chemotherapy (generally doxorubicin and ifosfamide)
based on prognostic factors predicting higher risk of
local recurrence and distant metastasis. Radiotherapy
was delivered through 8MV linear accelerator photon
to the target volume by two opposed fields, in a schedule
of 2 Gy/fraction, five fractions per week. An initial dose of
50Gy was delivered after surgical wound healing (within
8 weeks after surgery). Field borders were either the whole
compartment, or proximal and distal margins of 5 cm in
non-compartmental lesions and trunk. A cone-down field
of the original tumor bed plus 3 cm margins received an
additional boost (10–20Gy). Few patients did not receive
full dose RT for protecting organs at risk adjacent radiation field.
Follow-up
The items of follow-up included physical examination,
chest CT and ultrasonography of the primary site, with
additional MRI when local recurrence was suspected.
The patients were followed at 3-month interval for the
first 2 years, 6-month interval for the following 3 years
and yearly thereafter. The major endpoints of this study
were local recurrence, distant metastasis and overall survival. Local recurrence was defined as the first pathological verified tumor of the same histological type, within
or contiguous to the previously treated tumor bed at least
3 months after treatment. Distant metastasis was defined
by clinical, pathological or radiologic evidence of systemic
disease spread outside the primary tumor site.
Toxicity
Toxicities were evaluated by chart review using the Common Terminology Criteria for Adverse Events (CTCAE)
version 3.0. Only wound complications were recorded in
patients received surgery alone. The radiation-related
toxicities were recorded in patients received RT. The
highest grade of any observed toxicities reported for
each patient at the time of follow-up. Only ≥grade 2
toxicities were reported.
Statistical analysis
Descriptive data was compared using Pearson Chi-square
test or Fisher’s exact test, where appropriate. For survival
analysis, survival curves were constructed using the
Zhao et al. Radiation Oncology (2016):5
Kaplan-Meier method. The effect of demographic, clinical,
pathologic and treatment variables on survival were examined using the log-rank test to assess statistical difference. Multivariate analyses were performed using
Cox logistic regression method and P-value of <0.01
was included into multivariate analysis to fully identify
prognostic factors. A two-sided P-value of <0.05 determined statistical significance for all tests. All statistical
analyses were performed using SPSS 17.0 software package.
Page 3 of 8
Table 1 Patient, tumor and treatment characteristics (n = 240)
Characteristic
Number
Percent
≤50
114
51.8
>50
106
48.2
Male
132
60.0
Female
88
40.0
110
50.0
Age (years)
Gender
Location
Results
Patient characteristics
Patient, tumor, and treatment characteristics of study
population were listed in Table 1. The median age at
diagnosis was 50 years (range, 18–86 years) and 60 % of
patients were male. Exactly half tumors (110 cases,
50.0 %) were located in extremities, 52 (23.6 %) in trunk,
45 (20.5 %) in retroperitoneum and 13 (5.9 %) in head/
neck region. The most common histological subtype was
liposarcoma (41.4 %). The median tumor size was 7 cm
(range, 2–42 cm). RT was administered to 81 patients
(36.8 %). The radiation dose ranged from 45 Gy to
70 Gy, with a median dose of 60 Gy.
The patients were divided into RT group and no RT
group according to whether they received RT or not.
The distribution of the patient characteristics was listed
in Table 2. There were higher proportion of patients
with tumors located in the extremities and head/neck,
MFH, grade III, positive margin and the usage of chemotherapy in RT group, while the no RT group had a higher
rate of patients with tumors located in retroperitoneum,
liposarcoma, grade I and negative margin. The distribution of other clinicopathological factors was not significantly different between two cohorts (P >0.05).
Endpoints and survival analysis
Local failure-free survival
With a median follow-up of 68 months (range, 5–127
months), a total of 72 patients experienced local recurrence. Fifty-three patients had only local recurrence as
their initial site of failure, while in three patients, local
recurrence and distant metastases were detected concurrently. Of 53 patients with local recurrence as initial site
of treatment failure, the median time to local failure was
23 months (range, 3–126 months). The 5-year LFFS rate
was 70.0 %. In the multivariate analysis for LFFS, tumor
size, margin status and postoperative RT emerged as independent prognostic factors (p <0.05). Postoperative
RT significantly improved local control compared with
surgery alone [hazard ratio (HR) = 0.408, 95 % confidence interval (CI) 0.235–0.707, P = 0.001, Table 3],
with 5-year LFFS of 81.1 and 63.6 %, respectively (logrank, P = 0.004, Fig. 1a). Larger tumor size (HR = 1.815,
95 % CI 1.051–3.138 p = 0.033) and positive margin
Extremity
Trunk
52
23.6
Head/neck
45
20.5
Retroperitoneum
13
5.9
Histology
Rhabdomyosarcoma
27
12.3
Fibrosarcoma
23
10.5
MFH
54
24.5
Liposarcoma
90
40.9
Others
26
11.8
Tumor size (cm)
≤5
80
36.4
>5
140
63.6
I
31
14.1
II
58
26.4
III
131
59.5
Negative
195
88.6
Positive
25
11.4
Grade
Margin status
Lymph node status
Negative
210
95.5
Positive
10
4.5
No
179
81.4
Yes
41
18.6
No
139
63.2
Yes
81
36.8
Chemotherapy
Radiotherapy
(HR = 2.595, 95 % CI 1.432–4.702 p = 0.002) correlated
with worse outcome. The other clinicopathological factors were not significant in model.
Distant metastasis-free survival
Forty-eight patients developed distant metastases in this
study, including 30 patients with distant metastases only
and 18 patients with distant metastases and local recurrence as well. Of the 30 patients with distant metastases
Zhao et al. Radiation Oncology (2016):5
Page 4 of 8
Table 2 Distribution of patient, tumor and treatment
characteristics by receiving RT or not
RT
Characteristic
No RT
No.
%
No.
%
≤50
41
50.6
73
52.5
>50
40
49.4
66
45.5
Age (years)
P Value*
0.786
Gender
0.967
Male
49
60.5
83
59.7
Female
32
39.5
56
40.3
53
65.4
57
41.0
Location
Extremity
0.001
Trunk
15
18.5
37
26.6
0.191
Head/neck
11
13.6
2
1.4
<0.001
Retroperitoneum
2
2.5
43
30.9
<0.001
Rhabdomyosarcoma
12
14.8
15
10.8
0.400
Fibrosarcoma
8
9.9
15
10.8
0.831
MFH
28
34.6
26
18.7
0.010
Liposarcoma
22
27.2
68
48.9
0.002
Others
11
13.6
15
10.8
0.525
Histology
Tumor size (cm)
0.773
≤5
30
37.0
50
36.0
>5
51
63.0
89
64.0
I
4
4.9
27
19.4
0.002
II
21
25.9
37
26.6
1.000
III
56
69.1
75
54.0
0.033
Negative
66
81.5
128
92.1
Positive
15
18.5
11
7.9
Grade
Margin status
0.029
Lymph node status
75
92.6
135
97.1
Positive
6
7.4
4
2.9
No
59
72.5
120
86.3
Yes
22
27.2
19
13.7
Chemotherapy
Overall survival
A total of 65 deaths occurred during follow-up, including
60 patients who died of sarcoma-related causes. Other
causes of death included stroke (one patient), respiratory
failure (one), heart failure (one) and second cancers (two).
Of the 60 patients who died of sarcoma-related causes, 19
patients developed local recurrence only, 18 patients developed distant metastases only and 23 patients developed
both local recurrence and distant metastases. The 5-year
OS rate was 71.2 %. The univariate analysis showed RT
had a tendency of improving OS, with 5-year OS of 74.8
and 65.0 % in the RT group and no RT group, respectively
(P = 0.089, Fig. 1c). The multivariate analysis demonstrated that RT was associated with improved OS
(HR = 0.512, 95 % CI 0.296–0.886, p = 0.017, Table 3).
In the multivariate analysis, tumor size >5 cm was
also an independent significant adverse prognostic
factor compared to tumor size ≤5 cm, with a HR of
2.638 (95 % CI 1.392–4.998, p = 0.003). Additional adverse prognostic factor was positive margin status
(HR = 3.942, 95 % CI 2.233–6.959, p <0.001). Rhabdomyosarcoma was the worst histological subtype. Comparison
with rhabdomyosarcoma, patients with liposarcoma
(HR = 0.186, 95 % CI 0.088–0.392, p <0.001) and fibrosarcoma (HR = 0.142, 95 % CI 0.039–0.510, p = 0.003)
were associated with significant better survival.
The subgroup analysis on radiation effect
0.177
Negative
(95 % CI 0.033–0.661, p = 0.012) and 0.126 (95 % CI
0.056–0.303, p <0.001, Table 3), respectively. Although
univariate analysis showed grade, lymph node status and
chemotherapy were significant predictors for distant metastasis, these factors lost significant in the following Cox
logistic regression analysis (Additional file 1: Table S1).
0.019
Abbreviation: RT radiotherapy
*Determined by chi-square test
as initial site of treatment failure, the median time to
distant metastasis was 15 months (range, 3–114 months).
The 5-year DMFS rate was 78.2 %. The multivariate analysis showed that the significant predictor for distant metastasis was only histological subtype. Rhabdomyosarcoma
correlated with worst outcome, while fibrosarcoma and
liposarcoma predicted for better DMFS, with HR of 0.148
Local recurrence was developed in 21 of 81 patients
(25.9 %) who received RT and 51 of 139 patients
(36.7 %) who did not received RT, respectively. In RT
group, 13 patients developed local recurrence alone,
15 patients developed distant metastases alone, and
eight patients developed both local and distant failure.
In no RT group, 40 patients developed local failure
alone, 14 patients developed distant metastases alone
and 11 patients experienced both local and distant
failure. Postoperative RT significantly improved local
control compared with no postoperative RT (HR =
0.408, 95 % CI 0.235–0.707, P = 0.001, Table 3), with a
5-year actuarial LFFS of 81.1 and 63.6 %, respectively
(log-rank, P =0.004, Fig. 1a). The median time to local
recurrence in RT group and no RT group were 29 months
(range, 4–126 months) and 15 months (range, 3–120
months), respectively. The log-rank test showed that RT
postponed the time to local recurrence in patients who experienced local recurrence (P = 0.022). RT had no impact
Zhao et al. Radiation Oncology (2016):5
Page 5 of 8
Table 3 Multivariate analysis for LFFS, DMFS and OS
LFFS
Characteristic
HR (95 % CI)
DMFS
P*
HR (95 % CI)
OS
p
HR (95 % CI)
Age (>50 vs. ≤50)
0.980
0.774
0.210
Gender
0.602
0.780
0.794
Location
0.560
0.453
0.506
Histology
0.621
Rhabdomyosarcoma
<0.001
1.00
<0.001
1.00
Fibrosarcoma
0.128 (0.029–0.569)
0.012
0.142 (0.039–0.510)
0.003
MFH
0.574 (0.281–1.174)
0.088
0.516 (0.254–1.047)
0.067
Liposarcoma
0.161 (0.069–0.378)
<0.001
0.186 (0.088–0.392)
<0.001
Others
0.407 (0.154–1.074)
0.074
0.426 (0.169–1.073)
0.070
Tumor size (cm)
0.033
≤5
1.00
>5
1.815 (1051–3.138)
Grade
0.066
2.638 (1.392–4.998)
0.147
Margin status
0.259
0.002
Negative
1.00
Positive
2.595 (1.432–4.702)
0.003
1.00
0.400
0.143
1.00
<0.001
1.00
2.187 (1.055–4.536)
3.942 (2.233–6.959)
Lymph node status
0.909
0.272
0.582
Chemotherapy
0.687
0.894
0.719
Radiotherapy
0.001
0.769
0.017
No
1.00
1.00
Yes
0.408 (0.235–0.707)
0.512 (0.296–0.886)
Abbreviations: HR hazard ratio, CI confidence interval, OS overall survival, LFFS local failure-free survival, DMFS distant metastasis-free survival
*Determined by Cox logistic regression method
on the risk of development distant metastasis, with 5-year
DMFS of 73.1 and 80.8 % in the RT group and no RT
group, respectively (P = 0.307, Fig. 1b).
When we examined the impact of RT on OS, we
noted a tendency of improving OS, with 5-year OS of
74.8 and 65.0 % in the RT group and no RT group, respectively (P = 0.089 Fig. 1c). The multivariate analysis
demonstrated that RT was associated with improved
OS (HR = 0.512, 95 % CI, 0.296–0.886, p = 0.017, Table 3).
Only two patients with retroperitoneal STS received RT in
our study, which might bias the final survival results. We
excluded these patients with retroperitoneal STS and reanalyzed the efficacy of RT on OS. Multivariate analysis
confirmed that RT improved the OS (HR = 0.450, 95 % CI,
0.243–0.833, P = 0.011). We also performed univariate
analyses to identify specific subgroups of patients that
derived benefit from RT (Additional file 1: Table S2). The
result showed that RT significantly improved the 5-year
OS in the subset of patients with liposarcoma (90.9 % vs.
76.5 %, p = 0.041, Fig. 1d).
Toxicity
Sixteen of 139 patients (11.5 %) in the no RT group
compared to 13 of 81 patients (16.0 %) in the RT group
had ≥grade 2 wound complications. In the patients
received RT, 31 (38.3 %) patients suffered from ≥grade
2 radiation dermatitis. Late ≥grade 2 radiation-related
toxicities were recorded including peripheral nerve
damage, edema, joint stiffness and bone fracture. One
(1.2 %) patient developed radiation-related peripheral
nerve damage, 10 (12.3 %) patients had edema, 8 (9.9 %)
patients suffered from joint stiffness and bone fractures
were not seen.
Discussions
Our result showed that postoperative RT significantly
reduced the risk of local recurrence, while had no impact on development of distant metastasis. When we
examined the impact of postoperative RT on OS, we
noted RT had a tendency of improving OS. Multivariate
analysis demonstrated that RT was a significant prognostic factor for OS.
Randomized trials had demonstrated that postoperative radiotherapy could improve local control in patients
with STS when compared to surgery alone, especially in
patients with high grade tumor. Yang et al. showed that
postoperative RT significantly decreased the 10-year
local recurrence rate among patients with high-grade
Zhao et al. Radiation Oncology (2016):5
Page 6 of 8
Fig. 1 Kaplan-Meier estimates comparing patients receiving RT (RT group) and without receiving RT (No RT group) for a local failure-free survival;
b diatant metastasis-free survival; c overall survival; d overall survival in liposarcoma
lesions (no local recurrence in the RT group Vs 22 % in
no RT group, p = 0.0028) [6]. In another study, Adjuvant
brachytherapy improves local control after complete resection of soft tissue sarcomas in patients with high-grade
tumors, with the 5-year local control rate were 89 and
66 % in the RT and no RT group(p = 0.0025), respectively
[5]. The data from other retrospective studies also demonstrated that RT could improve local control in patients
with STS [8–10, 17, 18]. In our study, the effect of RT on
local control was in line with previous reports. Although
the impact of radiation on local control for extremity sarcoma has been well studied, the effects of local control on
survival are less well understood.
Multiple variety studies have examined the question of
survival benefit for postoperative RT in STS. However,
few of those studies had sufficiently power to detect a
survival advantage. Recently, several studies observed
that RT improved the survival of STS. In a study including 6960 patients with STS, Koshy et al. reported
that the 3-year overall survival rate was 73 % in the radiation group compared with 63 % in the no radiation
group (p <0.001). RT was associated with a significantly
improved OS (HR = 0.78, 95 % CI, 0.69–0.89) [12].
Schreiber et al. analyzed a cohort of 983 patients with
high-grade sarcoma. The authors found a survival benefit
at 3 years for patients with high-grade tumors >5 cm
Zhao et al. Radiation Oncology (2016):5
treated with radiotherapy (73.4 vs. 55.6 %, P <0.001) [19].
Kachare et al. found that RT was associated with a 5 % 5year survival advantage in a study including 2606 patients
with high-grade sarcoma of the extremity. The authors
concluded radiotherapy, regardless of the timing, was associated with improved survival in high-risk sarcoma [15].
In another study, Gutierrez et al. observed a statistically
significant increase in median overall survival of 3 months
in patients undergoing RT (p <0.001). Administration of
RT for high-grade lesions increased median survival to
25 months compared to only 16 months when RT was
not used (p <0.001) [20]. Alkis et al. found postoperative
RT was associated with significant improved OS in a
retrospective study including 294 patients with STS, with
5-year OS were 62.2 % and 32.1 % (P <0.0001) in patients
who received postoperative RT and surgery alone, respectively [13]. Another retrospective analysis of 202
patients with high grade STS of the extremity, brachytherapy following limb-sparing surgery resulted in favorable 5-year local control and OS rates [14]. All the
previous studies indicated RT could improve the survival
of patients with STS, which was in line with our results.
The scenario of RT improves survival can be interpreted
as the improvement of local control by RT translates into
survival benefit. In fact, the relationship between local control and prognosis of STS has long been debated. There
were many published studies showed that patients with
local recurrence had worse prognosis. The rationale may
be illustrated as follow. Firstly, RT may prevent further
tumor seeding by reducing local recurrence. Lewis et al.
analyzed the correlation of local recurrence with subsequent metastases in 911 patients with extremity STS. The
metastasis after local recurrence significantly increased in
patients with high-grade and deep tumors. They concluded
that there was a strong association of local recurrence with
the development of subsequent metastasis and tumor mortality [21]. Secondly, although the majority patients with
STS died of distant metastasis, local recurrence can also
directly influence survival. Gronchi et al. observed nearly
20 % of patients with STS receiving R1 resection died of
loco-regional recurrences without developing distant metastases [22]. Lewis et al. reported 84 of 112 (75 %) patients
with primary retroperitoneal STS died in the absence of
distant metastasis. The local recurrence rather than distant
metastasis was the primary cause of death [23]. A study
from M. D. Anderson Cancer Center (MDACC) reported
that a significant fraction of patients who died of STS (46
of 372 patients, 12 %) had only local recurrence. The authors believed that local recurrence was likely to influence
disease specific survival as well [24]. In our study, of 60 patients who died of cancer-related causes, 19 patients (32 %)
died of local recurrence without developing distant metastasis. The improvement of local control by using of RT has
potential take survival benefit in those patients.
Page 7 of 8
Sequencing of radiotherapy may also affect outcomes
in patients with STS. The only phase III randomized
study comparing preoperative to postoperative RT was
conducted by O’Sullivan et al. [25]. One hundred and
ninety patients were stratified by tumor size and randomized to preoperative (94 patients) or postoperative
RT (96 patients). Patients who had preoperative RT had
more wound complications than those receiving postoperative RT after treatment (35 % vs. 17 %, P = 0.01). However, at a median follow-up of 6.9 years, patients treated
with preoperative RT had a lower frequent of subcutaneous fibrosis (31.5 % vs. 48.2 %, P = 0.07), joint stiffness
(17.8 % vs. 23.2 %, P = 0.51), and edema (15.1 % vs. 23.2 %,
P = 0.26). There was no difference in terms of survival or
local, regional, and distant failure rates between the two
delivery methods [26]. Since acute wound complications
can be managed and are generally temporary whereas late
toxicities are longer lasting, preoperative RT is increasingly favored.
Histology, size, margin status and RT were identified as
significant prognostic factors for OS in our study, which
was generally in line with other reports. Stojadinovic et al.
identified that tumor size, grade, and resection margin
were significantly associated with sarcoma specific survival
in 2123 patients with completely resected localized primary STS [27]. Pisters et al. reported that tumor size,
grade, the histology, margin status and location were the
prognostic factors for disease specific survival [28]. Zagars
et al. studied the prognostic factors for disease specific
survival in patients with localized STS treated with conservative surgery and RT. They found that the independent factors that affected disease specific survival
were tumor grade, tumor size, tumor site, histopathology, patient age, and resection margins [24]. MarettyNielsen et al. established that age, size, grade, margin,
and radiotherapy were important prognostic factors for
both local recurrence and disease specific mortality in a
cohort study of 922 consecutive patients with STS [29].
Conclusion
STS is a disease largely limited to retrospective reports
given the paucity incidence. It is hard to study this disease systematically and therefore little information was
provided to assess the long-term benefits of RT. The
current study presented the outcomes of a single institution analysis of 220 patients with localized primary STS
treated by conservative strategy. Our study showed that
RT reduced local recurrence and had potential effect to
improve OS. With the limitations of a retrospective
database study, the results of our study suggested that
aggressive local therapy with RT followed by definitive
surgery may provide patients the opportunity for improved long-term survival. Prospective studies examining
the efficacy of RT on survival are necessary.
Zhao et al. Radiation Oncology (2016):5
Page 8 of 8
Additional file
Additional file 1: Table S1. Comparison of patient, tumor and treatment
factors for 5-year LFFS, DMFS and OS. Table S2. The subgroup analysis of
the impact of RT on OS. (DOCX 27 kb)
11.
12.
Abbreviations
CI: confidence interval; DMFS: distant metastasis-free survival; HR: hazard
ratio; IMRT: intensity-modulated radiation therapy; LFFS: local failure-free survival; OS: overall survival; RT: radiotherapy; STS: soft tissue sarcoma.
13.
14.
Competing interests
The authors declare that they have no competing interests.
15.
Authors’ contributions
R-PZ and X-LY carried out data collection, participated in analysis, helped draft
manuscript. ZZ, YF and carried out analysis and helped draft manuscript. L-JJ
involved in conceiving the study and participated in analysis. JW reviewed the
slides. Z-ZY and X-XC assisted with data collection. SLM and X-MG designed the
protocol, conceived he study and helped to draft the manuscript. All authors
read and approved the final manuscript.
Author details
1
Department of Radiation Oncology, Hangzhou Cancer Hospital, 34 Yan
Guan Lane, Hangzhou, Zhejiang, China. 2Department of Radiation Oncology,
Cancer Hospital of Fudan University, 270 Dong An Road, Xuhui, Shanghai,
China. 3Department of Oncology, Shanghai Medical College of Fudan
University, 270 Dong An Road, Xuhui, Shanghai, China. 4Department of
medical Oncology, Shandong Binzhou Central Hospital, 108 Southern
Huancheng Road, Binzhou, Shandong, China. 5Department of Pathology,
Cancer Hospital of Fudan University, 270 Dong An Road, Xuhui, Shanghai,
China. 6Department of Radiation Oncology, Hangzhou First People’s Hospital,
261 Huan Sha Road, Hangzhou, Zhejiang, China.
Received: 13 October 2015 Accepted: 18 February 2016
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